Investigating the Effect of Caffeine and Alcohol on Pupil Dynamics

Condition(s) studied

Investigational drug(s) / intervention(s)

Placebo Comparator: Placebo: Participants receive a matched placebo tablet together with a non-alcoholic beverage identical in appearance and volume to the active conditions. A cornstarch-based formulation may be used for the placebo tablet. Beverage presentation is standardized to maintain blinding across study conditions. No active caffeine or alcohol is administered.

Caffeine administration: Participants receive a single oral dose of caffeine (\~3 mg/kg body weight) administered in tablet form. The caffeine is given with a non-alcoholic beverage matched to study conditions. All procedures are performed under randomized, double-masked crossover design conditions.

Alcohol (Ethanol): Participants consume a standardized alcoholic beverage designed to achieve a target blood alcohol concentration of approximately 0.05%. A placebo tablet is administered alongside the beverage to maintain masking. All procedures are performed under randomized, double-masked crossover design conditions.

Study summary

The goal of this study is to understand how caffeine and alcohol affect the ocular and physiological systems, especially how the pupil (the aperture in the colored part of the eye) responds to light. It will also test whether these changes can be used to detect recent caffeine or alcohol intake using a portable eye device.

The main questions it aims to answer are:

1. How does caffeine change pupil responses, eye movements, and other ocular and physiological measurements?
2. How does alcohol change these same ocular and physiological responses?
3. Are the effects of caffeine and alcohol different from each other?
4. Can these changes be used to accurately identify whether someone has consumed caffeine or alcohol?

Researchers will compare caffeine, alcohol, and a placebo (a look-alike drink with no active substance) to see how each affects the ocular and physiological outcomes.

Participants will:

1. Attend three separate sessions where they will consume caffeine, alcohol, or a placebo (in random order)
2. Undergo pupillary response evaluation using a handheld device that measures responses to different colored light stimuli
3. Have their eye movements analyzed
4. Have retinal and choroidal thickness, blood perfusion, and ocular oxygen levels measured
5. Have basic body measurements recorded (such as pulse rate and blood pressure)
6. Complete tests at multiple time points over 2 hours after consumption

The results of this study may help develop a quick and non-invasive way to detect recent caffeine or alcohol use for clinical and safety purposes.

Eligibility

Primary outcome measure(s)

• Baseline Pupil Size — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Baseline pupil size will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Baseline pupil size refers to the resting pupil diameter measured prior to light stimulation. It is measured in pixels.
• Phasic Pupil Constriction to Blue Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Phasic pupil constriction to blue light will be quantified using handheld chromatic pupillometry. Phasic pupil constriction to blue light refers to the rapid, transient decrease in pupil diameter that occurs immediately after the onset of a blue light stimulus. It is calculated as a percentage change from baseline.
• Maximum Pupil Constriction to Blue Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Maximum pupil constriction to blue light will be quantified using handheld chromatic pupillometry. Maximum pupil constriction to blue light refers to the greatest reduction in pupil diameter observed following the onset of a blue light stimulus. It is calculated as a percentage change from baseline.
• Pupil Constriction Latency to Blue Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Pupil constriction latency to blue light will be quantified using handheld chromatic pupillometry. Constriction latency is defined as the time from blue light onset to the first detectable decrease in pupil diameter relative to baseline. It is measured in seconds or milliseconds.
• Phasic Pupil Constriction to Red Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Phasic pupil constriction to red light will be quantified using handheld chromatic pupillometry. Phasic pupil constriction to red light refers to the rapid, transient decrease in pupil diameter that occurs immediately after the onset of a red light stimulus. It is calculated as a percentage change from baseline.
• Maximum Pupil Constriction to Red Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Maximum pupil constriction to red light will be quantified using handheld chromatic pupillometry. Maximum pupil constriction to red light refers to the greatest reduction in pupil diameter observed following the onset of a red light stimulus. It is calculated as a percentage change from baseline.
• Pupil Constriction Latency to Red Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Pupil constriction latency to red light will be quantified using handheld chromatic pupillometry. Constriction latency is defined as the time from red light onset to the first detectable decrease in pupil diameter relative to baseline. It is measured in seconds or milliseconds.
• Phasic Pupil Constriction to Continuous White Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Phasic pupil constriction to continuous white light will be quantified using handheld chromatic pupillometry. Phasic pupil constriction to white light refers to the rapid, transient decrease in pupil diameter that occurs immediately after the onset of a white light stimulus. It is calculated as a percentage change from baseline.
• Maximum Pupil Constriction to Continuous White Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Maximum pupil constriction to continuous white light will be quantified using handheld chromatic pupillometry. Maximum pupil constriction to white light refers to the greatest reduction in pupil diameter observed following the onset of a white light stimulus. It is calculated as a percentage change from baseline.
• Pupil Constriction Latency to Continuous White Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Pupil constriction latency to continuous white light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Constriction latency is defined as the time from white light onset to the first detectable decrease in pupil diameter relative to baseline. It is measured in seconds.
• Maximum Pupil Constriction to White Light Flash — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Maximum pupil constriction to white light flash will be quantified using using handheld chromatic pupillometry. Maximum pupil constriction to white light refers to the greatest reduction in pupil diameter observed following the onset of a white light stimulus. It is calculated as a percentage change from baseline.
• Post-Stimulus Pupil Recovery Slope to Blue Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Post-stimulus pupil recovery slope to blue light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Post-stimulus pupil recovery slope refers to the rate of pupil re-dilation following the offset of a blue light stimulus. It is calculated as percentage change per second.
• Pupil Slope to Blue Light 1.7s before Blue Light Offset — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Pupil slope to blue light 1.7s before blue light offset will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Pupil slope to blue light within the last 1.7s refers to the rate of pupil re-dilation just before the offset of a blue light stimulus. It is calculated as percentage change per second.
• Pupil Slope to Blue Light 1.7s after Blue Light Offset — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Pupil slope to blue light in the 1.7s after blue light offset will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Pupil slope to blue light in the 1.7s after blue light offset refers to the rate of pupil re-dilation just after the offset of a blue light stimulus. It is calculated as percentage change per second.
• Post-Stimulus Pupil Recovery Slope to Red Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Post-stimulus pupil recovery slope to red light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Post-stimulus pupil recovery slope refers to the rate of pupil re-dilation following the offset of a red light stimulus. It is calculated as percentage change per second.
• Post-Stimulus Pupil Recovery Slope to White Light Flash — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Post-stimulus pupil recovery slope to white light flash will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Post-stimulus pupil recovery slope refers to the rate of pupil re-dilation following the offset of a white light stimulus. It is calculated as percentage change per second.
• Post-Stimulus Pupil Recovery Slope to Continuous White Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Post-stimulus pupil recovery slope to continuous white light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Post-stimulus pupil recovery slope refers to the rate of pupil re-dilation following the offset of a white light stimulus. It is calculated as percentage change per second.
• PIPR at 6 s - Blue Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Post-illumination pupillary responses (PIPR) to blue light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR at 6 s is measured as pupil size at 6 seconds after blue light offset. It is calculated as a percentage of baseline pupil size.
• PIPR at 12 s - Blue Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Post-illumination pupillary responses (PIPR) to blue light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR at 12 s is measured as pupil size at 12 seconds after blue light offset. It is calculated as a percentage of baseline pupil size.
• PIPR Area Under the Curve (0-12 s) - Blue Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Post-illumination pupillary responses (PIPR) to blue light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR area under the curve (AUC) from 0 to 12 seconds captures the total magnitude and duration of the sustained post-illumination response. It is calculated as the integrated area in %.s.
• PIPR at 6 s - Red Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Post-illumination pupillary responses (PIPR) to red light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR at 6 s is measured as pupil size at 6 seconds after red light offset. It is calculated as a percentage of baseline pupil size.
• PIPR Area Under the Curve - Red Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Post-illumination pupillary responses (PIPR) to red light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR area under the curve (AUC) from 0 to end of recording captures the total magnitude and duration of the sustained post-illumination response. It is calculated as the integrated area in %.s.
• PIPR at 6 s - Flash White Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Post-illumination pupillary responses (PIPR) to white light flash will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR at 6 s is measured as pupil size at 6 seconds after white light offset. It is calculated as a percentage of baseline pupil size.
• PIPR at 6 s - Continuous White Light — Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)
  Post-illumination pupillary responses (PIPR) to continuous white light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR at 6 s is measured as pupil size at 6 seconds after white light offset. It is calculated as a percentage of baseline pupil size.

Trial sites (1)

More National University of Singapore trials in Singapore